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Prediction of IgG1 ...
Prediction of IgG1 aggregation in solution.
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- Ojala, Frida (författare)
- Lund University,Lunds universitet,Avdelningen för kemiteknik,Institutionen för processteknik och tillämpad biovetenskap,Institutioner vid LTH,Lunds Tekniska Högskola,Division of Chemical Engineering,Department of Process and Life Science Engineering,Departments at LTH,Faculty of Engineering, LTH
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- Degerman, Marcus (författare)
- Lund University,Lunds universitet,Avdelningen för kemiteknik,Institutionen för processteknik och tillämpad biovetenskap,Institutioner vid LTH,Lunds Tekniska Högskola,Division of Chemical Engineering,Department of Process and Life Science Engineering,Departments at LTH,Faculty of Engineering, LTH
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Budde Hansen, Thomas (författare)
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Broberg Hansen, Ernst (författare)
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- Nilsson, Bernt (författare)
- Lund University,Lunds universitet,Avdelningen för kemiteknik,Institutionen för processteknik och tillämpad biovetenskap,Institutioner vid LTH,Lunds Tekniska Högskola,Division of Chemical Engineering,Department of Process and Life Science Engineering,Departments at LTH,Faculty of Engineering, LTH
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(creator_code:org_t)
- 2014-05-15
- 2014
- Engelska.
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Ingår i: Biotechnology Journal. - : Wiley. - 1860-6768. ; 9:6, s. 800-804
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Interest in monoclonal antibody aggregation is increasing as aggregates of biopharma-ceuticals can cause an immunogenic response when injected into the body. In this work a stoichiometric reaction model from concentration-time data is developed to predict the dimer ratio in stored antibody solutions over time. IgG1 was incubated at pH from 4.5 to 5.5, salt concentrations from 100 to 600 mmol/kg and protein concentrations of 10.6 to 26.3 g/l; samples were taken at intervals of 20 minutes to five hours over time periods from 4 hours to 7.6 days, and analyzed with size-exclusion chromatography. The experiments showed the formation of dimers from monomers, but no higher order aggregates. Dilution of samples containing dimers led to the reversal of the dimerization reaction. Measurements of the concentrations of each component were made by fitting exponentially modified Gaussian peaks to the chromatograms used to measure the concentrations of the different forms of protein. This stoichiometric reaction model was able to predict the formation of dimers by the antibody studied. The equilibrium constant was found to be dependent on the salt concentration, and the kinetic constant showed a dependence on the pH of the solution. The prediction of the aggregation leads to a possibility of optimizing the conditions in order to prevent the dimer formation and to maximize the monomer concentration.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Kemiteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Chemical Engineering (hsv//eng)
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